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• TITLE: GABAA Receptor Modulation by Compounds Isolated from Salvia triloba L.

  AUTHORS: Abeer Abdelhalim, Mary Chebib, Talal Aburjai, Graham A. R. Johnston, Jane R. Hanrahan

  KEYWORDS: GABAA Receptors; Salvia triloba; Flavonoids; Sedative; Anxiolytics; Chromatography; Allosteric Modulation

  JOURNAL NAME: Advances in Biological Chemistry, Vol.4 No.2, March 31, 2014

  ABSTRACT: Salvia triloba, traditionally known as Greek sage, has been used to enhance memory, as a sedative and to treat headaches. Pharmacological evaluation of purified extracts and isolated compounds of S. triloba were carried out on functional assays using two-electrode voltage clamp methods on recombinant GABA receptors expressed in Xenopus laevis oocytes. Bio-assay guided fractionation led to seven compounds being isolated from S. triloba: ursolic acid, carnosol, oleanolic acid, salvigenin, rosmanol, cirsimaritin and hispidulin. The purified extracts of S. triloba inhibited 54% of the current produced by 300 μM GABA at α1β2γ2L GABAA receptors. Ursolic acid, carnosol, oleanolic acid and rosmanol also acted as negative allosteric modulators. The flavonoids salvigenin, cirsimaritin and hispidulin acted as positive modulators when applied in the presence of low concentrations of GABA but in the presence of high concentrations of GABA acted as negative modulators, demonstrating a biphasic action. These results are consistent with the concept that Salvia triloba may have cognition enhancing properties. In most cases these activities are likely to be occurring via different modulatory sites on GABAA receptor complexes. It may be that the combination of these activities permits cognition enhancement whilst offering protection from convulsant activity.